Full thickness loss of articular cartilage will often progress in aging individuals until total destruction of a joint occurs. This in turn is extremely disabling, not only by limitation of function of a joint, but by producing severe pain. Left untreated, articular cartilage is not capable of repairing itself. On the basis of our prior research showing that perichondrial cells are capable of performing as chondroprogenitor repair cells, the focus of this research has evolved in the development of an optimized delivery system for treatment of an osteochondral defect. This delivery system consists of a porous polylactic acid (PLA) scaffold seeded with cells cultured from perichondrium. It is unknown whether such a repair system will give different results in skeletally mature vs aged animals. In addition, transforming growth factor (TGFbeta1) influences chondrocyte proliferation and the chondroid composition of the extracellular matrix (ECM), however its effect on repair in aged joints is unknown. The plasma cell membrane glycoprotein-1 (PC-1) gene has been postulated to regulate calcium deposition in the aging human chondrocyte; its influence on the ability of a cell to participate in a repair process in also unknown (Project 2). The current proposal has 4 specific aims: 1) To evaluate the repair of a full-thickness articular cartilage defect in skeletally mature and aged rabbits using a PLA scaffold seeded with cells grown from autologous perichondrium. 2) to assess the effect of transfection with the gene for PC-1 of the perichondrial cells used with the PLA scaffold and to determine the effect of this transfection on the repair of full-thickness cartilage defects in skeletally mature rabbits. 3) To assess the effect of transfection with the gene for TGFbeta1 of the perichondrial cells and its effect on repair when seeded into the PLA scaffold, and 4) To assess the long-term repairs of a full-thickness articular cartilage defect when treated with a PLA scaffold with or without autologous perichondrial cells with or without transfection with TGFbeta1. The assessment will be multidisplinary, employing: 1) Histomorphometric and immunohistochemistry measurements of neocartilage at the repair site. 2) Biochemical and molecular biological analysis of the expression of types I, II, and IX collagen genes. 3) Differential gene expression between the mRNA extracted from the progenitor chondroblastic cells with and without transfection with a plasmid containing TGFbeta1 gene of the mature and aged rabbits using differential display (DD) and representational difference analysis (RDA). 4) Biomechanical quantitation of neocartilage and subchondral tissue compressive material properties by confined compression testing with video microscopy, and host tissue integration by tensile testing to determine tissue tensile modulus.